This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Understanding of the central neural mechanisms mediating fever and cold defense will be relevant for developing therapeutic approaches to combat life-threatening excessive fevers (as during sepsis, toxemia, meningitis, some cancers) and to the management of the effects of thermal dysregulation that occurs during such clinically significant conditions as the abuse of amphetamine-based drugs, the hot flashes accompanying menopause and prostate surgery or the hypothermia induced during surgical anesthesia. The aims of this project are to elucidate the CNS circuits that regulate body temperature and how they are affected by pyrogens. Recent findings include the identification of a potent BAT sympathoinhibitory region in the ventrolateral medulla, the demonstration of a potent BAT excitatory effect following application of neuropeptide Y into the rostral raphe pallidus and the delineation of pathways controlling shivering thermogenesis. The required lentivirus and laser equipment have been obtained and lentivirus injections into the rat brainstem have been accomplished successfully.